Co-culture with chorionic villous mesenchymal stem cells promotes endothelial cell proliferation and angiogenesis via ABCA9-AKT pathway

FASEB J. 2022 Oct;36(10):e22568. doi: 10.1096/fj.202101316RR.


Human chorionic villous mesenchymal stem cells (CV-MSCs) are a promising and effective therapeutic option for tissue injury. Vascular dysfunction during pregnancies is significantly involved in the pathogenesis of preeclampsia (PE). This work aims to investigate how CV-MSCs regulate the function of vascular endothelial cells. In this study, RNA-seq analysis was used to examine the changes in HUVECs treated with CV-MSC conditioned medium (CM). We examined the levels of ABCA9 and AKT signaling in human umbilical vein endothelial cells (HUVECs) by immunohistochemistry, western blotting, and qRT-PCR assays. CCK-8, colony formation, and tube formation assays were used to understand the role of ABCA9 in HUVEC proliferation and angiogenesis mediated by CV-MSCs. The CV-MSC treatment significantly enhanced the HUVEC proliferation and angiogenesis. Furthermore, a significant increase in the ABCA9 expression and AKT pathway activation was observed in CV-MSCs -treated HUVECs. Consistent with these findings, ABCA9 overexpression exhibited the same proliferation-and angiogenesis-promoting effect in HUVECs as induced by CV-MSC CM, also accompanied the AKT signaling activation. In addition, inhibition of ABCA9 inactivated the AKT signaling in HUVECs and reduced the HUVEC proliferation and angiogenesis. Importantly, the elevation of proliferation and angiogenesis induced by ABCA9 overexpression in HUVECs could be reversed by AKT pathway inhibition. Our results suggest that ABCA9-dependent AKT signaling activation mediated by CV-MSCs could promote HUVEC proliferation and angiogenesis.

Keywords: ABCA9; AKT; CV-MSCs; HUVEC; preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Angiogenesis Inducing Agents / metabolism
  • Cell Proliferation
  • Coculture Techniques
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Female
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic
  • Pregnancy
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Sincalide / metabolism
  • Sincalide / pharmacology


  • ABCA9 protein, human
  • ATP-Binding Cassette Transporters
  • Angiogenesis Inducing Agents
  • Culture Media, Conditioned
  • Proto-Oncogene Proteins c-akt
  • Sincalide